A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers

Objective: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. Methods: Thirty subjects were administered a daily dose of either 5. mg donepezil or placebo for 15. days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. Results: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. Conclusion: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. Significance: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.